When taken orally the absorption depends on lipophilicity, with those with greater lipophilicity being absorbed more rapidly with a faster onset of action, however due to redistribution (i.e. to adipose tissue) these drugs have a shorter duration of action

Metabolism

Liver oxidation with the metabolites being conjugated to be excreted in the urine

Oxazepam, Lorazepam and Temazepam are directly conjugated (safer in those with liver disease, alcoholics)

Many metabolites are active with significant half-lives

Pregnancy: benzodiazepines cross the placenta and are present in breast milk

Drugs

Long acting

Diazepam (Valium)

Active metabolites (erratic availability IM)

5 mg PO (2-40 mg/day)

Chlordiazepoxide (Librium)

Active metabolities (erratic availability IM)

10-20 mg PO (5-300 mg/day)

Clonazepam (Rivotril)

0.25-4 mg/day

Flurazepam (Dalmane)

15-30 mg/day

Short acting

Lorazepam (Ativan)

No active metabolities

1-2 mg PO/SL; 0.5-2 mg IV (0.5-6 mg/day)

Alprazolam (Xanax)

Rapidly absorbed orally

0.25-0.5 mg PO (0.25-4 mg/day)

Temazepam (Restoril)

7.5-30 mg/day

Benzodiazepines are commonly used for treating the acute manifestations of Panic Disorder and General Anxiety Disorder (see psychiatry notes). They are recommended for short term use, and should be discontinued slowly in a tapering schedule.

Uses

Seizure control

Anxiety

Alcohol withdrawal

Insomnia

Agitation control

Muscle relaxants

Amnesia (i.e. procedural sedation)

Abuse potential

Short acting benzodiazepines have a higher abuse potential due to the rapid onset of action

Tolerance – requiring increased amount of drug to achieve a similar effect with ongoing use